FREQUENCY OF VKORC1 AND CYP2C9 GENES POLYMORPHISM IN ABKHAZIAN POPULATION.

The aim of the research was to study the frequency of VKROC1 and CYP2C9 genes different alleles for healthy donors and for patients with thrombosis, in Abkhazian population and to reveal the interdependence of the studied genes products in the treatment of thrombosis with warfarin. Warfarin is an anticoagulant, causing the inactivation of the VKORC1 gene product, which is one of the clotting factors. The protein product of CYP2C9 gene is involved in the metabolism of warfarin. Genotyping of blood samples for studied genes alleles was carried out using a tube scanner (ESE Quant Tube Scaner), allowing to identify SNPs. With the highest frequency in the studied group of healthy donors of Abkhazian population, by VKROC1 gene found Heterozygous (AG genotype) (74,5 %). The distribution of homozygous of "wild" (GG) and mutant genotype (AA) accounted for 13,5% and 11,8%, respectively. In the group of patients with Thrombosis, wild-type homozygotes accounted for 32.5%, which is significantly high compared to the control group. The percentage of heterozygotes was significantly lower than in the control group and accounted 56,25%. as for the homozygous mutant genotype, it was practically the same as in control group (11,2%). Regarding the rate of polymorphic variants of the CYP2C9 gene, quite large differences between diseased and healthy individuals were detected according to some of them. CYP2C9 *1/*1 genotype (wild- type homozygote) was observed in 32.9% of healthy individuals, while the same genotype was detected in only 14.5% of patients with thrombosis. The percentage of CYP2C9 *1/*2 genotype was slightly different between healthy and thrombotic subjects and corresponded to 27.5% in healthy individuals and 30.4% in thrombotic patients. CYP2C9 *1/*3 genotype accounted for 16.1% in healthy individuals. The mentioned indicator was significantly different from the similar indicator of patients with thrombosis, which corresponded to 24.1%. The largest difference between the percentages was observed according to the CYP2C9 *2/*3 (mutant heterozygote) genotype. In healthy individuals, this rate corresponded to 40.3%, and in thrombotic individuals - 11.4%. The CYP2C9 *2/*2 genotype was not observed in any of the study groups, while the percentage of CYP2C9 *3/*3 (mutant homozygous) individuals did not differ and amounted to 1.6% (in healthy individuals) and 1.2% (in thrombotic patients). VKORC1 and / or CYP2C9 genes polymorphisms are presented in a number of clinical dosing algorithms and in prospective clinical trials. In conclusion, it should be noted that the present work revealed a significant variability of genotypes between the groups of patients with thrombosis and healthy individuals, in Abkhazian population. The results obtained in determining the polymorphic variants of the VKORC1 and CYP2C9 genes, studied by us, should be taken into account when using algorithms to determine the optimal dosage for warfarin treatment in thrombotic individuals of the Abkhazian population, both during treatment and for the prevention of thrombosis.